Abstract

Background

Mechanisms involved in metabolic syndrome (MetS) development include insulin resistance,
weight regulation, inflammation and lipid metabolism. Aim of this study is to investigate
the association of single nucleotide polymorphisms (SNPs) involved in these mechanisms
with MetS.

Methods

In a random sample of the EPIC-NL study (n = 1886), 38 SNPs associated with waist circumference, insulin resistance, triglycerides,
HDL cholesterol and inflammation in genome wide association studies (GWAS) were selected
from the 50K IBC array and one additional SNP was measured with KASPar chemistry.
The five groups of SNPs, each belonging to one of the metabolic endpoints mentioned
above, were associated with MetS and MetS-score using Goeman’s global test. For groups
of SNPs significantly associated with the presence of MetS or MetS-score, further
analyses were conducted.

Results

The group of waist circumference SNPs was associated with waist circumference (P=0.03)
and presence of MetS (P=0.03). Furthermore, the group of SNPs related to insulin resistance
was associated with MetS score (P<0.01), HDL cholesterol (P<0.01), triglycerides (P<0.01)
and HbA1C (P=0.04). Subsequent analyses showed that MC4R rs17782312, involved in weight regulation, and IRS1 rs2943634, related to insulin resistance were associated with MetS (OR 1.16, 95%CI
1.02-1.32 and OR 0.88, 95% CI 0.79; 0.97, respectively). The groups of inflammation
and lipid SNPs were neither associated with presence of MetS nor with MetS score.

Conclusions

In this study we found support for the hypothesis that weight regulation and insulin
metabolism are involved in MetS development.MC4R rs17782312 and IRS1 rs2943634 may explain part of the genetic variation in MetS.